Delayed Onset of Autoreactive Antibody Production and M2-skewed Macrophages Contribute to Improved Survival of TACI Deficient MRL-Fas/Lpr Mouse

Overview

Journal Sci Rep

Specialty Science

Date 2018 Jan 24

PMID 29358664

Citations 8

Authors

Lunhua Liu

Windy Rose Allman

Adam Steven Coleman

Kazuyo Takeda

Tsai-Lien Lin

Mustafa Akkoyunlu

Affiliations

Soon will be listed here.

Abstract

Anti-B cell activating factor belonging to TNF-family (BAFF) antibody therapy is indicated for the treatment of patients with active systemic lupus erythematosus (SLE). We hypothesized that the BAFF receptor, transmembrane activator and calcium-modulator and cyclophilin interactor (TACI) may be responsible for the generation of antibody secreting plasma cells in SLE. To test this hypothesis, we generated TACI deficient MRL-Fas/Lpr (LPR-TACI-/-) mouse. TACI deficiency resulted in improved survival of MRL-Fas/Lpr mice and delayed production of anti-dsDNA and anti-SAM/RNP antibodies. There was also a delay in the onset of proteinuria and the accumulation of IgG and inflammatory macrophages (Mϕs) in the glomeruli of young LPR-TACI-/- mice compared to wild-type mice. Underscoring the role of TACI in influencing Mϕ phenotype, the transfer of Mϕs from 12-week-old LPR-TACI-/- mice to age-matched sick wild-type animals led to a decrease in proteinuria and improvement in kidney pathology. The fact that, in LPR-TACI-/- mouse a more pronounced delay was in IgM and IgG3 autoreactive antibody isotypes and the kinetics of follicular helper T (Tfh) cell-development was comparable between the littermates suggest a role for TACI in T cell-independent autoantibody production in MRL-Fas/Lpr mouse prior to the onset of T cell-dependent antibody production.

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References

Jacquemin C, Schmitt N, Contin-Bordes C, Liu Y, Narayanan P, Seneschal J . OX40 Ligand Contributes to Human Lupus Pathogenesis by Promoting T Follicular Helper Response. Immunity. 2015; 42(6):1159-70. PMC: 4570857. DOI: 10.1016/j.immuni.2015.05.012. View

Boghdadi G, Elewa E . Increased serum APRIL differentially correlates with distinct cytokine profiles and disease activity in systemic lupus erythematosus patients. Rheumatol Int. 2014; 34(9):1217-23. DOI: 10.1007/s00296-014-3020-4. View

Greenspan N, Lu M, Shipley J, Ding X, Li Q, Sultana D . IgG3 deficiency extends lifespan and attenuates progression of glomerulonephritis in MRL/lpr mice. Biol Direct. 2012; 7:3. PMC: 3293080. DOI: 10.1186/1745-6150-7-3. View

Schneider P, Mackay F, Steiner V, Hofmann K, Bodmer J, Holler N . BAFF, a novel ligand of the tumor necrosis factor family, stimulates B cell growth. J Exp Med. 1999; 189(11):1747-56. PMC: 2193079. DOI: 10.1084/jem.189.11.1747. View

Koyama T, Tsukamoto H, Miyagi Y, Himeji D, Otsuka J, Miyagawa H . Raised serum APRIL levels in patients with systemic lupus erythematosus. Ann Rheum Dis. 2004; 64(7):1065-7. PMC: 1755547. DOI: 10.1136/ard.2004.022491. View

Takahashi S, Nose M, Sasaki J, Yamamoto T, KYOGOKU M . IgG3 production in MRL/lpr mice is responsible for development of lupus nephritis. J Immunol. 1991; 147(2):515-9. View

Zhao L, Li Y, Smith Jr M, Wang J, Zhang W, Tang F . Expressions of BAFF/BAFF receptors and their correlation with disease activity in Chinese SLE patients. Lupus. 2010; 19(13):1534-49. DOI: 10.1177/0961203310375268. View

Vlahakos D, Foster M, Ucci A, Barrett K, Datta S, Madaio M . Murine monoclonal anti-DNA antibodies penetrate cells, bind to nuclei, and induce glomerular proliferation and proteinuria in vivo. J Am Soc Nephrol. 1992; 2(8):1345-54. DOI: 10.1681/ASN.V281345. View

Davidson A . What is damaging the kidney in lupus nephritis?. Nat Rev Rheumatol. 2015; 12(3):143-53. PMC: 4820834. DOI: 10.1038/nrrheum.2015.159. View

10.

Navarra S, Guzman R, Gallacher A, Hall S, Levy R, Jimenez R . Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: a randomised, placebo-controlled, phase 3 trial. Lancet. 2011; 377(9767):721-31. DOI: 10.1016/S0140-6736(10)61354-2. View

11.

Jacob C, Pricop L, Putterman C, Koss M, Liu Y, Kollaros M . Paucity of clinical disease despite serological autoimmunity and kidney pathology in lupus-prone New Zealand mixed 2328 mice deficient in BAFF. J Immunol. 2006; 177(4):2671-80. PMC: 2896675. DOI: 10.4049/jimmunol.177.4.2671. View

12.

Stein J, Lopez-Fraga M, Elustondo F, Carvalho-Pinto C, Rodriguez D, Gomez-Caro R . APRIL modulates B and T cell immunity. J Clin Invest. 2002; 109(12):1587-98. PMC: 151011. DOI: 10.1172/JCI15034. View

13.

Gross J, Johnston J, Mudri S, Enselman R, Dillon S, Madden K . TACI and BCMA are receptors for a TNF homologue implicated in B-cell autoimmune disease. Nature. 2000; 404(6781):995-9. DOI: 10.1038/35010115. View

14.

Hegazy M, Darwish H, Darweesh H, El-Shehaby A, Emad Y . Raised serum level of APRIL in patients with systemic lupus erythematosus: correlations with disease activity indices. Clin Immunol. 2010; 135(1):118-24. DOI: 10.1016/j.clim.2009.12.012. View

15.

Anders H, Appel G . Lupus nephritis: Implications of the new ACR lupus nephritis guidelines. Nat Rev Nephrol. 2012; 8(9):500-1. DOI: 10.1038/nrneph.2012.162. View

16.

Brannan C, Copeland N, Jenkins N, Nagata S . Lymphoproliferation disorder in mice explained by defects in Fas antigen that mediates apoptosis. Nature. 1992; 356(6367):314-7. DOI: 10.1038/356314a0. View

17.

von Bulow G, Van Deursen J, Bram R . Regulation of the T-independent humoral response by TACI. Immunity. 2001; 14(5):573-82. DOI: 10.1016/s1074-7613(01)00130-3. View

18.

Trager J, Ward M . Mortality and causes of death in systemic lupus erythematosus. Curr Opin Rheumatol. 2001; 13(5):345-51. DOI: 10.1097/00002281-200109000-00002. View

19.

Odegard J, Marks B, DiPlacido L, Poholek A, Kono D, Dong C . ICOS-dependent extrafollicular helper T cells elicit IgG production via IL-21 in systemic autoimmunity. J Exp Med. 2008; 205(12):2873-86. PMC: 2585848. DOI: 10.1084/jem.20080840. View

20.

Stohl W, Metyas S, Tan S, Cheema G, Oamar B, Xu D . B lymphocyte stimulator overexpression in patients with systemic lupus erythematosus: longitudinal observations. Arthritis Rheum. 2003; 48(12):3475-86. DOI: 10.1002/art.11354. View